Measles-Rubella Vaccine Immunogenicity at 6 and 9 Months of Age
Primary Purpose
Measles, Rubella, Rubella Syndrome, Congenital
Status
Completed
Phase
Phase 4
Locations
Bangladesh
Study Type
Interventional
Intervention
Measles-rubella (MR) vaccine at 6 and 9 months
Measles-rubella (MR) vaccine at 9 months
Sponsored by
About this trial
This is an interventional prevention trial for Measles focused on measuring measles, rubella, immunogenicity, congenital rubella syndrome, measles-rubella vaccine
Eligibility Criteria
Inclusion Criteria:
Infants:
- Healthy infants at 6 months (180 days, +/- 7 days) of age
- A parent or guardian that consents for participation in the full length of the study
- A parent or guardian that is able to understand and comply with planned study procedures
Inclusion criteria:
Mothers:
- Mothers of infants that meet inclusion criteria.
- ≥18 years of age
- Mothers who consent to participate in the full length of the study
Exclusion Criteria:
Infants:
- Family that is unable to participate in the full length of the study
- A diagnosis or suspicion of immunodeficiency disorder either in the infant or mother
- A diagnosis or suspicion of bleeding disorder that would contraindicate parenteral administration of MR vaccine or collection of blood by venipuncture
- Acute infection or illness at the time of enrolment (6 months ) that would require infant's admission to a hospital
- Receipt of any measles or rubella containing vaccine prior to enrolment (i.e., before age 6 months) outside of study based upon documentation or parental recall
- Known history of laboratory confirmed measles or rubella infection
- A diagnosis of rubella infection in mother during pregnancy
- A diagnosis of congenital rubella syndrome in infant
- Known allergy/sensitivity or reaction to measles-rubella containing vaccine or contents of measles-rubella containing vaccine
- Persons with a history of an anaphylactic reaction to any components of the vaccine
- Infants from premature births (<37 weeks of gestation)
Exclusion criteria: Mothers:
- Refuses to give blood samples. (If the mother agrees for her child to participate in the study, but refuses to give a blood samples herself or blood samples cannot be obtained, the child will still be enrolled.)
- A diagnosis or suspicion of immunodeficiency disorder
- A diagnosis or suspicion of bleeding disorder that would contraindicate collection of blood by venipuncture
Temporary exclusion:
Infants:
- Acute febrile illness (≥38°C) at the time of enrollment
- Family will be requested to bring back the child 1-2 days later or when child feels better.
Sites / Locations
- Icddr,B
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Group A:
Group B:
Arm Description
Group A will receive a measles-rubella vaccine dose at 6 and 9 months
Group B will receive a measles-rubella dose at 9 months only
Outcomes
Primary Outcome Measures
Seroconversion at 6 months
Measles neutralizing antibody titers (measured by plaque reduction neutralization test) and rubella titers (IU/mL) (measured by ELISA) on sera collected at 9 months of age. Seroprotection is defined as antibody level of ≥ 120 mIU/mL for measles and >10 IU/mL for rubella.
Seroconversion at 9 months
To assess immunogenicity of MR vaccine at 9 months of age among children without prior measles and rubella vaccination, compared with MR vaccine immunogenicity among those who had a prior MR vaccination at 6 months of age
Secondary Outcome Measures
Adverse Effects Following Immunization (AEFI)
To assess the frequency of adverse reactions following administration of MR vaccine at 6 months
Immunogenicity at 9 months
To compare the immunogenicity of the MR vaccine first dose administered at 6 months vs at 9 months
Measles and rubella titers of enrolled mothers
To assess the proportion of mothers with undetectable, detectable and protective levels of measles and rubella antibodies
Correlation of mothers' measles and rubella antibody levels with infants' maternal antibodies
To assess the correlation between measles and rubella antibody levels in women and levels of maternal antibodies in infants
Half-life and decay of maternal measles and rubella antibodies.
To estimate the half-life of decay of maternal measles and rubella antibodies in infants
Full Information
NCT ID
NCT03071575
First Posted
February 21, 2017
Last Updated
December 28, 2020
Sponsor
Centers for Disease Control and Prevention
Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh, Ministry of Health and Family Welfare, Bangladesh
1. Study Identification
Unique Protocol Identification Number
NCT03071575
Brief Title
Measles-Rubella Vaccine Immunogenicity at 6 and 9 Months of Age
Official Title
Assessing Immunogenicity of Measles-Rubella Vaccine at 6 and 9 Months of Age
Study Type
Interventional
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Completed
Study Start Date
March 9, 2017 (Actual)
Primary Completion Date
March 18, 2018 (Actual)
Study Completion Date
March 18, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Centers for Disease Control and Prevention
Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh, Ministry of Health and Family Welfare, Bangladesh
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is an open-label, randomized, 2-arm clinical trial in healthy infants in Bangladesh. The primary purpose of the study is to assess the immunogenicity of measles-rubella (MR) vaccine when delivered at 6 months. In addition, the study will establish the equality of MR vaccine seroconversion administered at 9 months following administration of an earlier MR vaccine dose at 6 months of age compared to MR vaccine dose administered at 9 months without previous MR vaccination. This study will also provide additional data on safety and tolerance of MR vaccine given at 6 months, and impact of maternal antibodies on immunogenicity of MR vaccine at 6 months.
Primary objectives:
To assess immunogenicity of MR vaccine at 6 months of age
To assess immunogenicity of MR vaccine at 9 months of age among children without prior measles and rubella vaccination, compared with MR vaccine immunogenicity among those who had a prior MR vaccination at 6 months of age
Secondary objectives
To assess the frequency of adverse reactions following administration of MR vaccine at 6 months
To compare the immunogenicity of the MR vaccine first dose administered at 6 months vs at 9 months.
To assess the proportion of mothers with undetectable, detectable and protective levels of measles and rubella antibodies
To determine the extent of variation in measles antibodies in women of child bearing age in a population with a long standing measles vaccination program
To determine the extent of variation in rubella antibodies in women of child bearing age in a population where rubella vaccine have been recently introduced
To determine if variation in antibody levels in infants at 6 months is predominately explained by variation in starting antibody levels in the mother in this population
To estimate the half-life of decay of measles and rubella antibodies in infants
Detailed Description
In countries with low levels of circulating measles virus, and lower risk for measles infection, measles containing vaccine first dose (MCV1) is recommended at 12 months of age. In countries with high risk for measles, MCV1 is recommended at 9 months. In the past decade, many countries have been experiencing measles outbreaks with a high proportion of cases among infants < 9 months of age, below the recommended age of routine MCV1.
Recent publications suggest that this may be due to the fact that the majority of infants now are born to mothers with vaccine induced immunity to measles, and who lose maternal antibodies much earlier, by age of 4-6 months. For example, in a measles outbreak in Malawi in 2010, 14% (17,858) of the estimated 134,000 cases occurred in children 0-8 months. In 2013, in a measles outbreak in Sri Lanka approximately 34% of measles cases were in children 6-12 months of age. Furthermore, in 2013 Jordan experienced a large measles outbreak with high proportion of young infants affected (6-9 months). WHO measles outbreak response guidelines recommend vaccinating children as young as 6 months during outbreaks. As an example, in response to a measles outbreak, Sri Lanka and Jordan conducted outbreak response immunization (ORI) that included infants 6 months of age despite the limited evidence on immunogenicity of MR vaccine at that age.
Some researchers suggest that routine MCV should be given before age of 9 months based on published data showing that infants born to mothers with vaccine induced measles immunity are born with lower concentration of maternal measles antibodies (MMA) and lose protection against measles infection at an earlier age. Measles vaccine immunogenicity depends on several factors, including presence of maternal measles antibodies (i.e., passively acquired measles antibodies may neutralize vaccine virus before a complete immune response develops resulting in primary vaccine failure.), maturity of immune system of the vaccine recipient, and strain of the measles vaccine used. So any decisions to alter the age of MCV1 dose should balance the potential risk of primary vaccine failure against the risk of measles infection and measles related complications, including death. Immunogenicity of measles vaccine given at 6 months is well studied; however, data on immunogenicity of combined MR vaccine administered at 6 months and its impact on MR vaccine effectiveness given at 9 months, is limited.
Because the number of infants born to mothers with vaccine induced immunity has been steadily increasing and most countries will be using MR vaccine routinely in the Expanded Program of Immunization (EPI), it is timely to conduct a study to assess immunogenicity of MR vaccine given at 6 months and its impact on a subsequent 9 month MR dose. The first dose of MCV given at 6 months is frequently referred to as MCV-0, indicating that two subsequent doses are needed to attain population seroprotection levels necessary to stop endemic transmission of the measles virus.
To improve the accuracy of interpretation of study results blood samples of mothers of enrolled infants will be tested for measles and rubella antibodies. This will also enable us to determine the proportion of mothers with undetectable, detectable and protective levels of antibodies, and to assess the relationship between the level of antibodies in mothers and their infants' maternal antibodies.
This study will be conducted in a single site in rural Bangladesh at Matlab. Matlab is a major rural field site for icddr,b, where for the past 50 years continuous health and demographic information was collected on >200,000 population.
From 2007 to 2010, icddr,b, the Ministry of Health (MOH) in collaboration with other international organizations conducted several randomized vaccine effectiveness studies.
This study will be an open-label, randomized, 2-arm clinical trial. 620 children will be enrolled and randomized at 6 months of age to one of two study arms. The primary objectives of this study are to assess the immunogenicity of MR vaccine at 6 months, and assess equality of MR vaccine seroconversion administered at 9 months following administration of an earlier MR vaccine dose at 6 months of age compared with MR vaccine dose administered at 9 months only without previous MR vaccination. The study will enroll generally healthy 6 month old infants living in Matlab and who have never received an MR vaccine dose and have no history of measles or rubella. Participants will be followed to 11 months of age.
Infants in this study will be randomly assigned to one of two arms. Infants in Study Arm A will receive MR vaccine at 6 months of age (at enrolment) and at 9 months. Infants in Study arm B will receive MR vaccine only at 9 months.
Blood specimens will be collected from all infants at 6, 9 and 11 months of age. The 6 month sample is a pre-vaccination sample and mainly will be used to determine maternal antibody levels. For arm A, the sample collected at 9 months before the second MR dose will be used to assess antibody levels after the first MR dose at 6 months of age. For study Arm B, the 9 month sample will be used to assess measles and rubella antibody decay rate. The sample collected at 11 months will be used to assess immune response to either a two dose or a one dose schedule (arms A and B, respectively).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Measles, Rubella, Rubella Syndrome, Congenital
Keywords
measles, rubella, immunogenicity, congenital rubella syndrome, measles-rubella vaccine
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Masking Description
Open label
Allocation
Randomized
Enrollment
620 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group A:
Arm Type
Active Comparator
Arm Description
Group A will receive a measles-rubella vaccine dose at 6 and 9 months
Arm Title
Group B:
Arm Type
Active Comparator
Arm Description
Group B will receive a measles-rubella dose at 9 months only
Intervention Type
Biological
Intervention Name(s)
Measles-rubella (MR) vaccine at 6 and 9 months
Other Intervention Name(s)
Arm A
Intervention Description
Arm A will receive MR vaccine dose at 6 and 9 months of age
Intervention Type
Biological
Intervention Name(s)
Measles-rubella (MR) vaccine at 9 months
Other Intervention Name(s)
Arm B
Intervention Description
Arm A will receive MR vaccine dose at 9 months of age
Primary Outcome Measure Information:
Title
Seroconversion at 6 months
Description
Measles neutralizing antibody titers (measured by plaque reduction neutralization test) and rubella titers (IU/mL) (measured by ELISA) on sera collected at 9 months of age. Seroprotection is defined as antibody level of ≥ 120 mIU/mL for measles and >10 IU/mL for rubella.
Time Frame
Change in antibody titers at 9 months compared to 6 months of age
Title
Seroconversion at 9 months
Description
To assess immunogenicity of MR vaccine at 9 months of age among children without prior measles and rubella vaccination, compared with MR vaccine immunogenicity among those who had a prior MR vaccination at 6 months of age
Time Frame
At 11 months of age.
Secondary Outcome Measure Information:
Title
Adverse Effects Following Immunization (AEFI)
Description
To assess the frequency of adverse reactions following administration of MR vaccine at 6 months
Time Frame
Day 1 to Day 84
Title
Immunogenicity at 9 months
Description
To compare the immunogenicity of the MR vaccine first dose administered at 6 months vs at 9 months
Time Frame
At 9 months and 11 months of age
Title
Measles and rubella titers of enrolled mothers
Description
To assess the proportion of mothers with undetectable, detectable and protective levels of measles and rubella antibodies
Time Frame
At day 1
Title
Correlation of mothers' measles and rubella antibody levels with infants' maternal antibodies
Description
To assess the correlation between measles and rubella antibody levels in women and levels of maternal antibodies in infants
Time Frame
Time from randomization to 9 and 11 months
Title
Half-life and decay of maternal measles and rubella antibodies.
Description
To estimate the half-life of decay of maternal measles and rubella antibodies in infants
Time Frame
Day 1 to day 84
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
11 Months
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Infants:
Healthy infants at 6 months (180 days, +/- 7 days) of age
A parent or guardian that consents for participation in the full length of the study
A parent or guardian that is able to understand and comply with planned study procedures
Inclusion criteria:
Mothers:
Mothers of infants that meet inclusion criteria.
≥18 years of age
Mothers who consent to participate in the full length of the study
Exclusion Criteria:
Infants:
Family that is unable to participate in the full length of the study
A diagnosis or suspicion of immunodeficiency disorder either in the infant or mother
A diagnosis or suspicion of bleeding disorder that would contraindicate parenteral administration of MR vaccine or collection of blood by venipuncture
Acute infection or illness at the time of enrolment (6 months ) that would require infant's admission to a hospital
Receipt of any measles or rubella containing vaccine prior to enrolment (i.e., before age 6 months) outside of study based upon documentation or parental recall
Known history of laboratory confirmed measles or rubella infection
A diagnosis of rubella infection in mother during pregnancy
A diagnosis of congenital rubella syndrome in infant
Known allergy/sensitivity or reaction to measles-rubella containing vaccine or contents of measles-rubella containing vaccine
Persons with a history of an anaphylactic reaction to any components of the vaccine
Infants from premature births (<37 weeks of gestation)
Exclusion criteria: Mothers:
Refuses to give blood samples. (If the mother agrees for her child to participate in the study, but refuses to give a blood samples herself or blood samples cannot be obtained, the child will still be enrolled.)
A diagnosis or suspicion of immunodeficiency disorder
A diagnosis or suspicion of bleeding disorder that would contraindicate collection of blood by venipuncture
Temporary exclusion:
Infants:
Acute febrile illness (≥38°C) at the time of enrollment
Family will be requested to bring back the child 1-2 days later or when child feels better.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
K. Zaman, MD
Organizational Affiliation
International Centre for Diarrhoeal Disease Research, Bangladesh
Official's Role
Principal Investigator
Facility Information:
Facility Name
Icddr,B
City
Chāndpur
Country
Bangladesh
12. IPD Sharing Statement
Learn more about this trial
Measles-Rubella Vaccine Immunogenicity at 6 and 9 Months of Age
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